The Effects of Imeglimin on Muscle Strength in Patients with Type 2 Diabetes: A Prospective Cohort Study.

INTRODUCTION: A bidirectional relationship has been observed between type 2 diabetes mellitus and sarcopenia, especially among older adults. While previous studies have reported that imeglimin improves mitochondrial function, they have not assessed its effects on muscle strength in patients with type 2 diabetes. Therefore, we aimed to investigate the effects of imeglimin on muscle strength in patients with type 2 diabetes. METHODS: In this prospective cohort study, we recruited consenting patients with type 2 diabetes (20-75 years). Changes in lean body mass (LBM), fat mass, quadriceps muscle strength, and grip strength from baseline (week 0) to week 24 were evaluated and compared between patients treated with imeglimin therapy (group I) and those who did not take imeglimin (controls, group C). RESULTS: We recruited 27 patients treated with imeglimin (group I) and 29 controls (group C), and 50 of them completed the study (group I: n = 23; group C: n = 27). The change in LBM, total body fat mass, or skeletal muscle index from baseline to week 24 did not differ significantly between the two groups. However, group I exhibited a significantly higher percent change in quadriceps knee extension strength from baseline to week 24 than group C (13 ± 19% and 2.1 ± 14%, p = 0.022). Conversely, the difference in percent change in grip strength was not significant. Multivariable analysis showed that imeglimin use was significantly associated with a percent change in quadriceps knee extension strength, independent of age, sex, body mass index, and skeletal mass index (ß = 0.325, p = 0.0014). CONCLUSIONS: Imeglimin positively affected muscle strength in patients with type 2 diabetes without altering LBM. Therefore, imeglimin exerts a unique effect on skeletal muscles in humans. Further randomized controlled trials are needed to validate these findings. TRIAL REGISTRATION: This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000054715).

Distinguishing coagulase-negative Staphylococcus bacteremia from contamination using blood-culture positive bottle detection pattern and time to positivity.

AIM: Detection of coagulase-negative Staphylococcus in blood culture may be a result of either bacteremia or contamination. This often leads to diagnostic uncertainly. Our objective was to develop a method for differentiating whether a coagulase-negative Staphylococcus sp. positive blood culture represents bacteremia or contamination based on positive bottle detection pattern and time to positivity (TTP). METHODS: This study included 155 and 51 adults with positive blood cultures for Staphylococcus epidermidis and Staphylococcus hominis, respectively, over a three-year period from 2016 to 2018. Positive blood culture cases were categorized as either bacteremia or contamination based on the clinically available information, and the detection pattern and TTP in each category were investigated. RESULTS: A total of 57, 92, and 6 S. epidermidis positive blood cultures were categorized as bacteremia, contamination, and undetermined, respectively, whereas 15 and 36 S. hominis positive blood cultures were categorized as bacteremia and contamination, respectively. For positive blood cultures categorized as bacteremia, all four bottles in two sets of blood cultures were positive in 47/47 S. epidermidis and 14/14 S. hominis, respectively, whereas either one bottle in each of two sets or three bottles in two sets were positive in 10/19 S. epidermidis and 1/4 S. hominis, respectively; most of those TTPs were <48 h. Among them, the TTP in catheter-related blood stream infection was <24 h. CONCLUSION: Although clinical assessment is crucial to differentiate between bacteremia and contamination, a combination of positive bottle detection pattern and TTP is a valuable diagnostic auxiliary tool.

Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH. METHODS: Twelve newborn C57BL/6 J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured. RESULTS: Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 µmol/L, P = 0.001). CONCLUSIONS: FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production.